%0 Journal Article
%A Barilla, Rocky M
%A Berard, Clara
%A Sun, Linyu
%A Sandhu, Sumiti
%A Zaghouani, Sarah
%A Iyer, Krishna S
%A Altun, Gizem
%A Su, Chien-Wen
%A Deguine, Jacques
%A Singh, Vasundhara
%A Hou, Yu
%A Kusumakar, Kanupriya
%A Rutlin, Michael L
%A Rao, Meenakshi
%A Zaghouani, Habib
%A Shi, Hai Ning
%A Xavier, Ramnik J
%A Kuchroo, Vijay K
%T Type 2 cytokines act on enteric sensory neurons to regulate neuropeptide-driven host defense.
%J Science
%V 389
%N 6757
%@ 0036-8075
%C Washington, DC
%I American Association for the Advancement of Science
%M DKFZ-2025-01066
%P 260-267
%D 2025
%Z 2025 Jul 17;389(6757):260-267
%X Enteric nervous system (ENS)-derived neuropeptides modulate immune cell function, yet our understanding of how inflammatory cues directly influence enteric neuron responses during infection is considerably lacking. Here, we characterized a primary enteric sensory neuron (PSN) subset producing the neuropeptides neuromedin U (NMU) and calcitonin gene-related peptide β (CGRPβ) and coexpressing receptors for the type 2 cytokines interleukin-4 (IL-4) and IL-13. Type 2 cytokines amplified NMU and CGRPβ expression in PSNs, in vitro and in vivo, which was abrogated by PSN-specific Il13ra1 deletion. Deletion of Il13ra1 in PSNs impaired host defense to the gastrointestinal helminth Heligmosomoides polygyrus and blunted muscularis immune responses. Co-administration of NMU23 and CGRPβ rescued helminth clearance deficits and restored anti-helminth immunity, highlighting the essential bi-directional neuro-immune crosstalk regulating intestinal type 2 inflammation.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40403128
%R 10.1126/science.adn9850
%U https://inrepo02.dkfz.de/record/301545